3-Nitropropionic acid depresses spinal reflexes involving GABAergic and glycinergic transmission in neonatal rat spinal cord in vitro.
OBJECTIVE
3-Nitropropionic acid (3-NPA) is a naturally occurring fungal toxin that leads to ATP-depletion by inhibiting mitochondrial succinate dehydrogenase and produces chemical anoxia. The present study was conducted to identify the involvement of inhibitory system in 3-NPA-induced depression of spinal reflexes.


METHODS
The monosynaptic (MSR) and polysynaptic reflex (PSR) potentials were recorded at ventral root by stimulating the corresponding dorsal root in hemisected (sagitally) spinal cord from 4-8 day old rats. Effect of 3-NPA in the absence and presence of antagonists was evaluated on the reflexes.


RESULTS
Superfusion of 3-NPA (3.4 mM) depressed the reflexes in a time-dependent manner abolishing them by 35 min. The T-50 values were around 18 and 16 min for MSR and PSR, respectively. An NMDA receptor antagonist, DL-2-amino-5-phosphonovaleric acid (10 microM) failed to block the 3-NPA (3.4 mM)-induced depression of reflexes. Superfusion of bicuculline (GABAA receptor antagonist; 1 microM), or strychnine (glycineA receptor antagonist; 1 microM) antagonized the 3-NPA-induced depression of reflexes significantly. The T-50 values were 26 and 30 min in bicuculline and strychnine pretreated groups, respectively and were significantly greater than 3-NPA only group.


CONCLUSIONS
The results indicate that 3-NPA-induced depression of spinal reflexes is partially mediated by GABAergic and glycinergic inhibitory transmission.
Gupta
Rajesh
R
Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, UP, India.
Deshpande
Shripad B
SB
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000502:physiology*; D018684:Glycine Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009574:Nitro Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011422:Propionates / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D012018:Reflex / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018684:Glycine Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D005680:gamma-Aminobutyric Acid; D015763:2-Amino-5-phosphonovalerate; D013331:Strychnine; C015392:3-nitropropionic acid; D005998:Glycine; D001640:Bicuculline